Abstract:

Background: Linezolid standard dosing is fixed at 600 mg q12h for adults. Literature suggests critically-ill, obese patients require higher doses. The study aim is two-fold: (i) to describe linezolid PK and (ii) to evaluate if PK/PD target attainment is achieved with standard dosing in critically-ill, obese patients with severe SSTIs.

Methods: Adult patients with a body mass index (BMI) ≥ 30 kg/m2 and receiving IV linezolid from August 2018 to April 2019 were eligible for consent in this prospective study. Severe SSTIs were defined as necrotizing fasciitis, myonecrosis, or SSTI with sepsis syndrome. Four blood samples were collected at steady state at 1, 3, 5 hours post-infusion and as a trough. Target attainment was defined as achieving AUC0-24h/MIC ≥ 100 hr*mg/L. Monte Carlo simulations were used to determine probability of target attainment (PTA).

Results: Eleven patients were included in the study. The median BMI was 45.7 kg/m2 and median total body weight (TBW) was 136.0 kg. Seven patients received standard linezolid doses and four received 600 mg q8h. A one-compartment model described linezolid PK. Based on AUC0-24h/MIC targets, for non-cirrhotic patients at 140 kg, PTA with standard linezolid doses was 100%, 98.8%, 34.1%, and 0% for MICs 0.5, 1, 2, and 4 mg/L, respectively.

Conclusion: Target attainment ≥ 90% is not achieved with standard linezolid doses for non-cirrhotic patients ≥ 140 kg with MICs ≥ 2 mg/L. This study adds to accumulating evidence that standard linezolid doses may not be adequate for all patients.

Reference:

Blackman AL, Jarugula P, Nicolau DP, Chui SH, Joshi M, Heil EL, Gopalakrishnan M. Evaluation of linezolid pharmacokinetics in critically-ill obese patients with severe skin and soft tissue infections. Antimicrob Agents Chemother. 2020 Nov 30:AAC.01619-20. doi: 10.1128/AAC.01619-20. Epub ahead of print. PMID: 33257446.